The objective of the proposed studies is to analyze the cellular and humoral aspects of the secretory immune response manifested by the appearance of IgA-associated antibodies to antigens of S. mutans in glandular secretions of man and animals. The effectiveness of the oral route of antigen-administration in inducing a secretory immune response, and the increasing evidence for the existence of the common mucosal immune system in man provide a reasonable basis for an approach to human immunization. Because B cells that localize in the salivary glands may originate in gut-associated lymphoid tissue, and occur also in peripheral blood, we shall study the in vitro response of peripheral blood lymphocytes from individuals orally immunized with S. mutans. After stimulation with polyclonal mitogens or with selected antigens of S. mutans, the numbers of cells engaged in the production of anti-S. mutans, antibodies, and the characteristics of these antibodies (class, IgA subclass and molecular forms) will be determined. The properties of naturally- occurring anti-S. mutans antibodies in external secretions and sera of individuals of various age will be investigated with respect to immunoglobulin class, IgA subclass, molecular form and specificity toward selected S. mutans antigens such as glucosyltransferase, surface proteins and serotype-specific carbohydrate. Systemic immunization of rodents with immune complexes composed of various model antigens and corresponding IgA antibodies will be explored as a possible means of inducing a selective IgA response in external secretions. Factors that can potentially affect the differentiation of B cells into immunoglobulin-producing cells will be studied. Specifically, the polyclonal activation of human B cells by Fc fragments derived from IgA by the action of IgA protease from S. sanguis and the effect of saliva and salivary proteins on the mitogen-induced differentiation of B cells will be investigated.